cdc.gov/coronavirus

Adaptive immunity and SARS-CoV-2

Natalie J. Thornburg, Ph.D

Lead respiratory virus immunology

ACIP

September 22, 2021
Outline

 Adaptive cellular and humoral immunity

 Correlates and contributors to immunity

 Immune durability

 Age-related immunosenescence

 Variant circulation might affect immunity

 Conclusions
Adaptive cellular and humoral immunity
Adaptive immunity includes cellular and humoral 

responses

https://www.virology.ws/2020/11/05/t-cell-responses-to-coronavirus-infection-are-complicated/
Antibodies decay with a known half-life

Immunoglobulin Approximate halflife (days)

IgM 5-6

IgA 5-6

IgG1 21

IgG2 21

IgG3 7

IgG4 21
Memory T and B cells are generated, which can 

initiate anamnestic responses after re-exposure

Roda et al. Cell
Immunity – correlates and contributors
Immunity is a gradient

Sterilizing

Hospitalization / Death

Asymptomatic

Symptomatic URI

Symptomatic LRI

Mild symptomatic URI

Antibody levels

Antibody isotypes

Antibody functionality 

(neutralizing / epitopes / affinity)

Antibody location

Number and specificity T cells

T cell ratios

Levels of immunity Contributors

URI – upper 

respiratory tract 

infection

LRI – lower 

respiratory tract 

infection
Transfer of IgG with high neutralization titer is 

sufficient to protect against SARS-CoV-2 challenge of 

rhesus macaques

Lower respiratory tract

https://doi.org/10.1038/s41586-020-03041-6
Anti-spike antibodies are correlates of risk

• Khourey et al. normalized neutralizing antibody titers after vaccination with 

different vaccine products to mean convalescent titers. Used these 

normalized values to compare vaccine efficacy (VE) estimates. Used the 

normalized values to estimate the level of neutralizing antibodies required 

for 50% protection against infection.

• Goldblatt et al. assayed binding and neutralization in participants who had 

received BNT162b, mRNA1272, AZD1222, or Ad26Cov2.S and used a 

population-based method to estimate a protective threshold (60 BAU/ml 

anti-spike IgG).

• Feng et al. calculated the levels binding and neutralizing antibodies required 

for 50, 60, 70, 80, and 90% VE from symptomatic infection after vaccination 

with AZD1222.
Correlates analysis of mRNA-1273 indicates 68% of VE 

mediated through serum neutralizing antibodies

 Day 29 and Day 57 correlates analysis examining inhibitory concentrations 

50% (IC50) with neutralization assays

 VE was estimated to be 45 – 60% for vaccine recipients without detectable 

binding or neutralizing antibodies

 Increased to >98% VE in recipients with highest neutralization titers

 Analysis estimated 68% of VE against symptomatic infection was mediated 

through Day 29 neutralization titers

Gilbert et al. medRxiv
Correlates studies focus on humoral arm of adaptive 

immunity, but that is not the only contributor

≈ 68% ≈ 32%

Roda et al. Cell
In previously infected macaques with low levels of 

antibodies, CD8+ T cells contribute to protection

McMahan et al. Nature 

Upper respiratory tract
What happens during infections in vaccinated people?

Sterilizing

Hospitalization / Death

Asymptomatic

Symptomatic URI

Symptomatic LRI

Antibody levels

Antibody isotypes

Antibody functionality 

(neutralization / epitopes / 

affinity)

Antibody location

Number and specificity T cells

T cell ratios
Culturable virus recovered from unvaccinated and 

vaccinated infected health care workers 

Shamier et al. medRxiv
Immune durability
Anti-spike antibodies decay after BNT162b2 

vaccination

Naber et al. The Lancet Regional Health - Europe Maeda et al. medRxiv
mRNA vaccine recipients maintain spike-specific 

memory B cells at 6 months

Goel et al. bioRxiv

Moderna Pfizer-BioNTech

Ciabattini et al. medRxiv
BNT162b2 mRNA vaccine recipients generate spikespecific early memory CD8+ T cells

Oberhardt et al. Nature
Durability

 Serum antibodies decrease over time

 Memory B cells are maintained out to 6 months post-vaccination

 Early memory CD8+ T cells are detected >80 days after vaccination with 

BNT162b2
Immunosenescence
Pool of naïve T cells diminished with age

Candia et al. Trends in Immunology
Adaptive immunity includes cellular and humoral 

responses

https://www.virology.ws/2020/11/05/t-cell-responses-to-coronavirus-infection-are-complicated/
Adults ≥80 years have reduced neutralization titers 

compared to younger adults after BNT162b2 

vaccination 

Probability of + 

neutralization after 1 dose

Collier et al. Nature
Adults ≥ 80 years had less mature antibodies and 

fewer functional T cells after BNT162b2 vaccination

B cells T cells

Collier et al. Nature
Variants
Decay of neutralizing antibodies could be confounded 

by circulation of variants of concern

Liu et al. Nature

• Some variants have amino acid 

changes near the spike receptor 

binding domain that could result 

in reduction in neutralization 

titers.

• Neutralization loss ranges from 

nil (alpha) to about 7-fold (beta). 

Delta is approximately 1.5-2-fold 

reduction. Eta Kappa Delta Delta
Antibody decay plus reduction in neutralization titers 

yield lower titers at six months after mRNA-1273 

boost

Pegu et al. Science
Reduced titers in older adults can also be further 

confounded by variant circulation

Collier et al. Nature Pegu et al. Science

Peak BNT162b2 Six months mRNA-1273
T cell activity maintained against variant spikes after 

BNT162b2 vaccination

Richardson et al medRxiv
Summary
Conclusions 1 of 3

 There are degrees of protection from different outcomes based on a 

person’s level of immunity.

 Multiple components of the immune system are required to prevent infection 

and illness; these components are complex and dynamic.

 When a vaccinated person becomes infected, they may shed culturable 

virus, and therefore may be infectious.
Conclusions 2 of 3

 Antibodies decrease over time in all age groups; cellular memory is 

maintained after waning.

 Neutralizing antibodies likely confer a majority of, but not all, immunity.

 Cellular responses likely contribute to protection against severe disease 

through anamnestic response even after antibodies wane.
Conclusions 3 of 3

 Older adults 

– Start with lower neutralization titers than younger adults.

– Because they start at lower titers, they may be faster to fall below the 

lower limit of detection.

– May have less robust cellular memory generation because of 

immunosenescence and therefore may be more dependent on 

humoral immunity.

– Reduced neutralization of variant viruses may confound antibody 

waning in all age groups.
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The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.